| Popis: |
The antifolate combination of pyrimethamine (PM) and sulfadoxine (SD) [PM/SD] has increasingly become the drug of choice for the treatment of uncomplicated malaria in Africa. PM is an inhibitor of dihydrofolate reductase (DHFR), which is one component of a bifunctional protein with thymidylate synthetase (DHFR-TS) (1). SD is thought to act against dihydropteroate synthase (DHPS), a bifunctional protein combined with hydroxymethypterin pyrophosphokinase (2, (3). The synergistic activity of these 2 compounds lead to the inhibition of tetrahydrofolate synthesis, an essential cofactor for 1-C transfer reactions that leads to the synthesis of deoxythymidylate monophosphate (dTMP) and methionine. Wherever PM/SD has been used, the emergence and the spread of resistance have been rapid. This is what happened in South East Asia and South America (4) where this drug were in use some decades back. The same rapid pace of selection of resistant parasites is also predicted in sub-Saharan Africa (5), (6), (7). In this paper, we summarised the current data on the mechanism of PM/SD resistance. |
